Multifunctional Tumor-Targeting Nanocarriers Based on Hyaluronic Acid-Mediated and pH-Sensitive Properties for Efficient Delivery of Docetaxel
Multifunctional Tumor-Targeting Nanocarriers Based on Hyaluronic Acid-Mediated and pH-Sensitive Properties for Efficient Delivery of Docetaxel
复制标题
基于透明质酸介导和 pH 敏感特性的多功能肿瘤靶向纳米载体，可有效输送多西紫杉醇
DOI：
10.1007/s11095-013-1225-y
复制
发表时间：
2014-04-01
影响因子：
3.7
通讯作者：
Pan, Weisan
中科院分区：
文献类型：
--
作者：
Song, Shuangshuang;Chen, Fen;Pan, Weisan
PurposeThe objective of this work was to develop a multifunctional tumor-targeting nanocarrier based on the mechanism of CD44-mediated endocytosis and pH-induced drug release to improve the therapeutic efficacy of docetaxel (DTX).MethodsHyaluronic acid-coated docetaxel-loaded cholesteryl hemisuccinate vesicles (HA-CHEMS vesicles) were prepared. The physiochemical properties and pH-dependent drug release of HA-CHEMS vesicles were evaluated. The HA-CHEMS vesicles were investigated for CD44-mediated internalization andin vitrocell viability using MCF-7,A549 and L929 cells.In addition,tissue distribution as well as antitumor efficacy was also evaluated in MCF-7 tumor-bearing mouse model.ResultsThe particle size and zeta potential of HA-CHEMS vesicles were 131.4 ± 6.2 nm and −13.3 ± 0.04 mV,respectively. Thein vitrodrug release results demonstrated a pH-responsive drug release under different pH conditions.In vitrocell viability tests suggested that the encapsulation of DTX in HA-CHEMS vesicles led to more than 51.6-fold and 46.3-fold improved growth inhibition in MCF-7 and A549 cell lines,respectively compared to Taxotere®. From the cell uptake studies,the coumarin 6-loaded HA-CHEMS vesicles enhanced intracellular fluorescent intensity in the CD44-overexpressing cell line (MCF-7). Biodistribution studies revealed selective accumulation of HA-CHEMS vesicles in the MCF-7 bearing BalB/c nude mice as a result of passive accumulation and active targeting (CD44-mediated endocytosis). Compared to Taxotere®,HA-CHEMS vesicles exhibited higher antitumor activity by reducing tumor volume (P< 0.05) and drug toxicity,demonstrating the success of the multifunctional targeting delivery.ConclusionsThis work corresponds to the preparation of a multifunctional tumor-targeted delivery system. Our investigation shows that hyaluronan-bearing docetaxel-loaded cholesteryl hemisuccinate vesicles (HA-CHEMS vesicles) is a highly promising therapeutic system,leading to tumor regression after intravenous administration without visible toxicity.
